Rare variant tests

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Summary of rare variant tests for sequence data

Compiled by Cristen Willer and Suzanne Leal for the ESP Feb 1, 2011

* indicates applicability to quantitative data

? indicates possible applicability to quantitative data with adaptation Blue font indicates implementation in upcoming PLINKSeq release (http://atgu.mgh.harvard.edu/plinkseq/)

Will be implemented in PlinkSeq

1) Aggregate tests using a cut off e.g. 1 % analyzing nonsynonymous variants to detect detrimental variants

Test Name Reference Software Notes
CMC/T1 test* Li & Leal, 2008
KBAC Liu & Leal, 2010
VT* Price et al., 2010 http://genetics.bwh.harvard.edu/rare_variants/
WSS Madsen & Browning, 2009
CMAT Zawistowski et al. 2010
ANRV/GRANVIL* Morris & Zeggini
RARECOVER Bhati et al. 2010
CCRaVAT and QuTie* Lawrence et al. 2010 http://www.sanger.ac.uk/resources/software/rarevariant/
RVE (rare variant exclusive) Cohen & Hobb

2) Aggregate tests for protective and detrimental variants (recommend 1% cutoff)

Test Name Reference Software Notes
C-alpha [Neale et al., submitted]
Ionita-Laza & Lange Ionita-Laza & Lange, 2011
DASH* Han & Pan
SKAT* Wu et al., 2010 http://www.hsph.harvard.edu/~xlin/software.html
WHaIT Li et al. 2010 http://www.sph.umich.edu/csg/yli/whait/
EMMPAT* King et al. 2010 http://home.uchicago.edu/~crk8e/papersup.html

3) Analyzing common and rare variants together (could down-weight or threshold common variants)

Test Name Reference Software Notes
WSS Madsen & Browning, 2009
RARECOVER Bhati et al. 2010
Step-Up Collapsing* Hoffman et al. 2010
CMC/T5 test* Li & Leal, 2008
MENDEL* Zhou et al. 2011 http://www.genetics.ucla.edu/software/download?package=1

4.) Analyze higher frequency rare variants >1% individually

                  Use same regression frame work which has been used for common variants*
                  Use meta analysis to combine results from sequence data and imputed genotypes to increase power*


Additional tests Test Name Notes Reference Website/Code Logic Regression* Kooperberg et al. (2001) http://kooperberg.fhcrc.org/papers/2001gaw.pdf Sequence diversity Anderson (2006) Sequence dissimilarity* Schork et al. (2008), Wessel et al. (2006) Ridge Regression* Malo et al. (2008)


Additional tests

Test Name Reference Software Notes
Logic regression* Kooperberg et al. 2001
Sequence diversity Anderson et al. 2006
Sequence dissimilarity* Schork et al. 2008, Wessel et al. 2006
Ridge regression * Malo et al. 2008